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Biomedical subjects

Jun Zhang

Publications and source records attributed to Jun Zhang.

At least 163 records · Page 9Linked to original sources
PubMed2005

Cross-inhibition to heterologous foot-and-mouth disease virus infection induced by RNA interference targeting the conserved regions of viral genome.

RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells. In mammalian cells, RNAi can be triggered by 21-23 nucleotide duplexes of small interfering RNA (siRNA). Strategies to inhibit RNA virus multiplication based on the use of siRNAs have to consider the high genetic polymorphism exhibited by this group of virus. Here we described a significant cross-inhibition of foot-and-mouth disease (FMD) virus (FMDV) replication in BHK-21 cells by siRNAs targeted to various conserved regions (5'NCR, VP4, VPg, POL, and 3'NCR) of the viral genome. The results showed that siRNAs generated in vitro by human recombinant dicer enzyme gave an inhibition of 10- to 1000-fold in virus yield of both homologous (HKN/2002) and heterologous (CHA/99) isolates of FMDV serotype O at 48 h post-infection (hpi). The inhibition extended to at least 6 days post-infection. For serotype Asia1, the virus yield in YNBS/58-infected cells examined at 12, 24, and 48 hpi decreased by approximately 10-fold in cells pretreated with HKN/2002-specific siRNAs, but there was no significant decrease at 60 hpi. The inhibition was specific to FMDV replication, as no reduction was observed in virus yield of pseudorabies virus, an unrelated virus. Moreover, we also demonstrated an enhanced viral suppression could be achieved in BHK-21 cells with siRNA transfection after an infection had been established. These results suggested that siRNAs directed to several conserved regions of the FMDV genome could inhibit FMDV replication in a cross-resistance manner, providing a strategy candidate to treat high genetic variability of FMDV.

3' Untranslated Regions↗
PubMed2005

Hydrophobicity of reactive site loop of SCCA1 affects its binding to hepatitis B virus.

AIM: To investigate the role of SCCA2 and other SCCA1 molecules in the process of hepatitis B virus (HBV) binding to mammalian cells. METHODS: SCCA1 and SCCA2 were isolated from HepG2. Binding protein (BP) genes were obtained through PCR. Recombinant baculoviruses expressing SCCA1, SCCA2, BP, and different mutants were constructed and utilized to infect mammalian cells to investigate the binding ability of infected cells to HBV. RESULTS: A SCCA1 gene (A1) was isolated from HepG2, but it appeared to lack the binding ability of infected cells to HBV. Two mutants, A1-BP and BP-A1, were constructed by interchanging the carboxyl terminal of A1 and BP. Cells expressing A1-BP showed an increased virus binding capacity, but not BP-A1. Comparison of A1 sequence with the sequence of BP indicated the presence of only three amino acid changes in the carboxyl terminal, two of them were found in the reactive site loop (RSL) of SCCA1. Primary structure assay revealed that the hydrophobicity of BP and AJ515706 in this domain was strong, but A1 was relatively weak. Changing the aa349 of A1 from low hydrophobic glutamic acid to high hydrophobic valine enhanced HBV binding. In contrast, HBV binding was reduced by changing the aa349 of BP from valine to glutamic acid. CONCLUSION: The results suggest that the hydrophobicity of RSL of SCCA1 may play an important role in HBV binding to cells.

Antigens, Neoplasm↗
PubMed2005

Identification of candidate regions for familial idiopathic scoliosis.

STUDY DESIGN: A genomic screen and statistical linkage analysis of 202 families with at least two individuals with idiopathic scoliosis was performed. OBJECTIVES: To identify candidate regions or the autosomal loci that may be involved in the expression of familial idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: A large sample of families with individuals having idiopathic scoliosis (202 families; 1,198 individuals) was ascertained; diagnoses were based on physical examination and radiographic criteria. METHODS: Model-independent linkage analysis of qualitative and quantitative traits (degree of lateral curvature) related to scoliosis was used to screen genotyping data from 391 markers in the 202 families. Subsets of families were determined before genotyping based on the most likely mode of inheritance for each family (autosomal dominant vs. X-linked dominant). Fine mapping results corroborated linkage in the primary candidate regions. RESULTS: Candidate regions on chromosomes 6, 9, 16, and 17 were considered to have the strongest evidence for linkage across all subsets considered. CONCLUSION: Linkage analyses have identified several candidate regions, a significant step in defining the genetic etiology of this disorder.

Family↗
PubMed2005

Potent and specific inhibition of SARS-CoV antigen expression by RNA interference.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease caused by SARS-CoV. There are no effective antiviral drugs for SARS although the epidemic of SARS was controlled. The aim of this study was to develop an RNAi (RNA interference) approach that specifically targeted the N gene sequence of severe acute respiratory syndrome associated coronavirus (SARS-CoV) by synthesizing short hairpin RNA (shRNA) in vivo, and to assess the inhibitory effect of this shRNA on SARS-CoV N antigen expression. METHODS: The eukaryotic expression plasmid pEGFP-C1-N, containing SARS-CoV N gene, was co-transfected into 293 cells with either the RNAi plasmid pshRNA-N or unrelated control plasmid pshRNA-HBV-C4. At 24, 48 and 72 hours post transfection, the green fluorescence was observed through a fluorescence microscope. The RNA levels of SARS-CoV N were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression of Green Fluorescent Protein (GFP) and protein N were detected using Western blot. RESULTS: The vector, pshRNA-N expressing shRNA which targeted the N gene of SARS-CoV, was successfully constructed. The introduction of RNAi plasmid efficiently and specifically inhibited the synthesis of protein N. RT-PCR showed that RNAs of N gene were clearly reduced when the pEGFP-C1-N was cotransfected with pshRNA-N, whereas the control vector did not exhibit inhibitory effect on N gene transcription. CONCLUSIONS: Our results demonstrate that RNAi mediated silencing of SARS-CoV gene could effectively inhibit expression of SARS-CoV antigen, hence RNAi based strategy should be further explored as a more efficacious antiviral therapy of SARS-CoV infection.

Antigens, Viral↗
PubMed2005

An imaging study using laminin peptide 99mTc-YIGSR in mice bearing Ehrlich ascites tumour.

BACKGROUND: The YIGSR is a pentapeptide, from the laminin-1 of the beta1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of (99m)Tc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour. METHODS: Using S-acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with (99m)Tc. (99m)Tc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged. RESULTS: Through reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. (99m)Tc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P < 0.001). CONCLUSIONS: Using S-acetly-NH3-MAG3, we radiolabelled YIGSR with (99m)Tc. (99m)Tc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest (99m)Tc-YIGSR is a promising tumour radiotracer.

Animals↗
PubMed2005

Probing conformational changes of proteins by quantitative second-derivative infrared spectroscopy.

Probing protein conformational changes plays a crucial role in protein structure and function studies. However, the lack of efficient biophysical techniques makes it difficult to obtain the distinct behaviors of different secondary structure elements in a protein upon perturbation. This paper presents a discussion of the two major problems, the effect of sidelobes and different half-width at half-height (HWHH) values, encountered in quantitative second-derivative infrared (QSD-IR) spectroscopy and introduces the development of two criteria for checking the validity of the results obtained using the QSD-IR method. It was found that neither the sidelobes nor the HWHH significantly affected the quantitative result of protein conformational changes by using poly-l-lysine and hemoglobin as model proteins. A case study of bovine serum albumin (BSA) thermal aggregation suggested that the thermal transition of BSA was a process involving sequential events, and the two helical components were found to have a distinct response to heat perturbation. These results were confirmed by two-dimensional infrared correlation spectroscopy and by results in literature, suggesting that the QSD-IR method might be a potentially powerful tool to probe the distinct response of different secondary structures to perturbation.

Animals↗
PubMed2005

A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates.

It was evaluated its antigenicity, immunogenicity and efficacy of a candidate recombinant hepatitis E virus (HEV) vaccine, referred hitherto as HEV 239 vaccine. The vaccine peptide has a 26 amino acids extension from the N terminal of another peptide, E2, of the HEV capsid protein, which has been shown to protect monkeys against HEV infection previously. The vaccine peptide is similar as E2 in that: first, the vaccine peptide migrates predominantly as dimer in SDS-PAGE and it is dissociated into monomers by heating; second, its dimeric form of which predominantly recognized by HEV reactive human serum; and third, it shows the same pattern of reaction as E2 with a panel of eight monoclonal antibodies that had been raised against E2. In contrast to E2, the vaccine peptide aggregates to form particles of 13 nm mean radius, and consequently, it is more than 240 times more immunogenic than E2. Using alum as adjuvant, immunizing dose determined in mice was 80-250 ng for the vaccine and >60 microg for E2. Rhesus monkeys twice vaccinated with a 10 microg or a 20 microg formulation of this vaccine showed essentially the same antibody response, whereas the response to a 5 microg formulation was delayed but reached similar antibody levels. All the three vaccine formulations afford complete protection against infection with 10(4) genome equivalent dose of the homologous genotype 1 virus. At higher virus dose of 10(7), the same vaccine formulation partially protected against the infection and completely protected against hepatitis. The efficacy of the vaccine was essentially the same for the homologous genotype 1 virus and heterologous genotype 4 virus.

Animals↗
PubMed2005

Analysis of hepatitis E virus neutralization sites using monoclonal antibodies directed against a virus capsid protein.

The dimeric form of the recombinant peptide (E2), comprising amino acid 394-606 of the capsid protein of hepatitis E virus (HEV), is strongly recognized by HEV reactive human serum, and when used as a vaccine, it protects rhesus monkeys against experimental HEV infection. In this work, the relationship of E2 to HEV has been probed using three murine monoclonal antibodies, 8C11, 13D8 and 8H3, all of which react predominantly against the E2 dimer, and can effect immune capture of the virus as well. 8C11 and 8H3 were further found to neutralize HEV infectivity in animals. Cross-blocking patterns between these antibodies discerned two spatially separate antigenic domains, one identified by 8C11 and 13D8, and the other, by 8H3. Kinetic studies using BIAcore biosensor suggest that the epitope to which 8H3 is directed is partially masked, and thus has limited access by the native antibody. However, this is not the case with the smaller Fab. Access to the 8H3 epitope was enhanced by the binding of 8C11, and inhibited by the binding of 13D8 to a distal site on the peptide. Similar to the effects of binding 8H3 to E2, 8C11 was found to enhance immune capture by 8H3, while 13D8 was inhibitory. Moreover, 8C11 and 8H3 act synergistically to neutralize HEV infectivity. The parallel cross-reaction patterns that these antibodies exhibit against the peptide and the virus, respectively, implicate two interacting conformationally dependent neutralization sites on the HEV particle. These sites might cooperate in the adsorption and penetration of the HEV virus.

Animals↗
PubMed2005

Transcription factor Sp1 expression in gastric cancer and its relationship to long-term prognosis.

AIM: To explore the expression of Sp1 in gastric carcinoma as well as its association with other clinicopathologic features, and to evaluate the role of Sp1 as a prognostic indicator of gastric carcinoma. METHODS: By using immunohistochemistry, we examined the Sp1 expression patterns in 65 cases of human gastric cancer, and 40 normal gastric mucosa specimens. Simultaneously, the correlation between Sp1 expression and clinical outcome or clinicopathologic features was investigated. RESULTS: The percentage of Sp1 expression was 12.5% (5/40) in normal gastric mucosa, and the Sp1 protein was mainly expressed in the nuclei of cells located in the mucous neck region. In sharp contrast, strong Sp1 expression was detected in tumor cells, whereas no or faint Sp1 staining was detected in stromal cells and normal glandular cells surrounding the tumors. The expression rate of Sp1 in gastric cancer lesions was 53.85% (35/65). The medium survival duration in patients who had a tumor with negative, weak and strong Sp1 expressions was 1 700, 1 560 and 1 026 d, respectively (P<0.05). Sp1 protein expression was closely related to the depth of tumor infiltration (chi(2) = 13.223, P<0.01) and TNM stage (chi(2) = 11.009, P<0.05), but had no relationship with the number of lymph nodes and Lauren's classification (P>0.05). Cox regression model for multivariate analysis revealed that high Sp1 expression (P<0.05) and advanced stage (P<0.01) were independent predictors of poor survival. CONCLUSION: Normal and malignant gastric tissues have unique Sp1 expression patterns. Sp1 might serve as an independent prognostic factor, by influencing the tumor infiltration and progression.

Adenocarcinoma↗
PubMed2005

Cloning and characterization of mouse homolog of the CXC chemokine receptor CXCR1.

CXCR2/IL-8RB was the only receptor previously reported in mice for ELR+ CXC chemokines, whereas the receptors for these chemokines in human include both CXCR1 and CXCR2. In this study, we cloned the full length cDNA of the mouse CXCR1 (mCXCR1) gene. The deduced amino acid of mCXCR1 was 77% and 58% identical to the rat and human CXCR1, respectively. RT-PCR and Northern blot analysis showed that mCXCR1 mRNA was expressed in lung, spleen, thymus, peripheral blood leukocytes, as well as in the isolated neutrophils. In a mouse respiratory inflammation model induced by lipopolysaccharide, a large number of neutrophils infiltrated into the lung and, meanwhile, the mCXCR1 expression was significantly increased in the recruited neutrophils, suggesting that mCXCR1 may mediate the recruitment of neutrophils to the inflammation site under certain infections.

Amino Acid Sequence↗
PubMed2005

Experimental free-space distribution of entangled photon pairs over 13 km: towards satellite-based global quantum communication.

We report free-space distribution of entangled photon pairs over a noisy ground atmosphere of 13 km. It is shown that the desired entanglement can still survive after both entangled photons have passed through the noisy ground atmosphere with a distance beyond the effective thickness of the aerosphere. This is confirmed by observing a spacelike separated violation of Bell inequality of 2.45+/-0.09. On this basis, we exploit the distributed entangled photon source to demonstrate the Bennett-Brassard 1984 quantum cryptography scheme. The distribution distance of entangled photon pairs achieved in the experiment is for the first time well beyond the effective thickness of the aerosphere, hence presenting a significant step towards satellite-based global quantum communication.

Journal Article↗
PubMed2005

Tumor vaccine based on cell surface expression of DcR3/TR6.

DcR3/TR6, a secreted protein belonging to the TNF receptor superfamily, interacts with lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entrance mediator (LIGHT), Fas ligand (FasL), and TL1A, all members of the TNF superfamily. Solid-phase TR6 can trigger reverse signaling of LIGHT and FasL expressed on T cells, and lead to T cell costimulation. In this study, we engineered tumor cells to express cell surface TR6 and used these cells as a tumor vaccine. We demonstrated that mastocytoma P815 cells expressing surface TR6 (TR6-P815) effectively augmented the T cells response in vitro and ex vivo in terms of proliferation, as well as IL-2 and IFN-gamma secretion. TR6-P815 cells had reduced tumorigenicity compared with parental P815 cells. When inactivated TR6-P815 cells were employed as a vaccine, they protected the mice from challenge with live parental P815 cells, and eliminated established P815 tumors. The cell surface TR6-based tumor vaccine was also effective against low antigenicity tumors, such as B16 melanoma; co-administration of bacillus Calmette-Guérin further enhanced the vaccine's efficacy. Thus, cell surface TR6 expression is a useful addition to our tumor vaccine arsenal.

Animals↗
PubMed2005

Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor.

The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases liver size. Here we show that CAR-mediated hepatomegaly is a transient, adaptive response to acute xenobiotic stress. In contrast, chronic CAR activation results in hepatocarcinogenesis. In both acute and chronic xenobiotic responses, hepatocyte DNA replication is increased and apoptosis is decreased. These effects are absent in CAR null mice, which are completely resistant to tumorigenic effects of chronic xenobiotic stress. In the acute response, direct up-regulation of Mdm2 expression by CAR contributes to both increased DNA replication and inhibition of p53-mediated apoptosis. These results demonstrate an essential role for CAR in regulating both liver homeostasis and tumorigenesis in response to xenobiotic stresses, and they also identify a specific molecular mechanism linking chronic environmental stress and tumor formation.

Animals↗
PubMed2005

Heavy flags undergo spontaneous oscillations in flowing water.

By immersing a compliant yet self-supporting sheet into flowing water, we study a heavy, streamlined, and elastic body interacting with a fluid. We find that above a critical flow velocity a sheet aligned with the flow begins to flap with a Strouhal frequency consistent with animal locomotion. This transition is subcritical. Our results agree qualitatively with a simple fluid dynamical model that predicts linear instability at a critical flow speed. Both experiment and theory emphasize the importance of body inertia in overcoming the stabilizing effects of finite rigidity and fluid drag.

Journal Article↗
PubMed2005

[Effect of weight loss induced by laparoscopic adjustable gastric banding on immunity of morbid obesity].

OBJECTIVE: To compare the immunity of morbid obesity (MO) before and after laparoscopic adjustable gastric banding (LAGB). METHODS: 15 cases, with a mean body mass index (BMI) of 35.8 kg/m(2), were treated by LAGB from Jun. 2003 to Oct. 2003 in our department. Patients' immune parameters were determined preoperatively and 1, 3 and 6 months postoperatively. 15 cases with a normal BMI (23.6 kg/m(2)) were set as controls. RESULTS: Before surgery, the MO had a significant lower level of CD(4)(+), CD(4)(+)/CD(8)(+) and a higher level of serum interleukin-2 (IL-2), Interleukin-6 (IL-6) than the controls (P < 0.01). There was a significant reduction of weight and BMI 6 months postoperatively (P < 0.01). At the same time, CD(4)(+) increased and serum IL-2 decreased significantly. But CD(4)(+)/CD(8)(+)and serum IL-2, IL-6 were still abnormal compare to the controls. CONCLUSIONS: MO may combined with an abnormal immunity. But after enough weight loss induced by LAGB, it can be partly reversed.

Adolescent↗
PubMed2005

Relationship between expression and distribution of cyclooxygenase-2 and bcl-2 in human gastric adenocarcinoma.

AIM: To explore expression and distribution features of COX-2 and bcl-2 in human gastric adenocarcinoma tissues and to study its biological significance. METHODS: Totally 36 human gastric carcinoma samples were enrolled in this study (cardiac adenocarcinoma 16 cases, distal gastric adenocarcinoma 20 cases). The expressions of COX-2 and bcl-2 in cancerous tissues and corresponding para-cancerous tissues were investigated by immunohistochemistry using COX-2 polyclonal antibody and bcl-2 monoclonal antibody. The normal gastric mucosa tissues were used as control. RESULTS: The expressions of COX-2 and bcl-2 in gastric carcinoma were significantly higher than that in the para-cancerous tissues (77.8% vs 47.2%, P<0.01, 80.56% vs 58.33%, P<0.05). The expression of COX-2 in cardiac adenocarcinoma was remarkably higher than that in the distal gastric carcinoma (93.8% vs 65.0%, P<0.01). The expression of COX-2 was mainly localized in the cytoplasm of tumor cells and partly in the nucleus. There is a transition of the COX-2 cytoplasmic positivity to nucleic in tumor cells with the increase of gastric carcinoma pathological grade. Interstitial macrophages, fibroblasts and vascular endothelial cells also expressed COX-2. The tissues with higher expression of COX-2 also expressed high level of bcl-2 protein. CONCLUSION: Abnormal expression pattern of COX-2 within the tissues of human gastric cancer is correlated with tumor location and lymph node metastasis. COX-2 may regulate expression of apoptosis suppressor gene (bcl-2) through interaction of tumor cells and stromal cells and play an important role in the generation and development of tumors, which will be of great help in developing new methods for antitumor therapy.

Adenocarcinoma↗
PubMed2005

Energetics and structural consequences of axial ligand coordination in nonplanar nickel porphyrins.

The effects of ruffling on the axial ligation properties of a series of nickel(II) tetra(alkyl)porphyrins have been investigated with UV-visible absorption spectroscopy, resonance Raman spectroscopy, X-ray crystallography, classical molecular mechanics calculations, and normal-coordinate structural decomposition analysis. For the modestly nonplanar porphyrins, porphyrin ruffling is found to cause a decrease in binding affinity for pyrrolidine and piperidine, mainly caused by a decrease in the binding constant for addition of the first axial ligand; ligand binding is completely inhibited for the more nonplanar porphyrins. The lowered affinity, resulting from the large energies required to expand the core and flatten the porphyrin to accommodate the large high-spin nickel(II) ion, has implications for nickel porphyrin-based molecular devices and the function of heme proteins and methyl-coenzyme M reductase.

Crystallography, X-Ray↗